Tumor-specific antigens serve as targets for the immune system of the host and may play a role in establishing the malignant phenotype of the tumor cell. The long term objective of the proposed research is to understand the genetic and epigenetic mechanisms by which the tumor cell regulates expression of its tumor-specific antigens. Antigenic variants of murine lymphomas growing in tissue culture will be used to study the genetics of tumor cell antigens. Somatic genetic analysis will be used to establish the number, dominance, and nature of the genes controlling the expression of several model antigens. Nongenetic alteration of surface antigen expression (antigenic modulation) will be studied in tumor antigen systems using radiolabeled antibody techniques.